Research topics Schulz-Heddergott lab
Department of Molecular Oncology
Identification of distinct pathway regulations by specific p53 mutants in colorectal (CRC) and pancreatic cancer (PDAC)
The tumor suppressor p53 is subject to the most frequent mutations across all cancer species. We explore gain-of-function (GOF) activities of specific missense p53 mutants (misp53) in gastrointestinal cancers. Importantly, some p53 missense mutants can gain GOF activities that are not automatically shared by other mutants. A prerequisite for misp53 GOF activities is the protein stabilization of p53 mutants by the HSP90 system. Recently, we discovered that the misp53R248Q/W GOF mutant increases tumor growth and invasiveness in CRC and PDAC. We proceed our studies within the Clinical Research Unit 5002 ‘Deciphering Genome Dynamics for Subtype-specific Therapy in Pancreatic Cancer’.
Exploration of disordered proteins during cancer progression and as vulnerability in cancer therapies
Failures in the HSF1-HSP90 system can lead to intrinsically disordered, aggregated proteins and are associated with neurodegenerative diseases. More recently, evidence emerged that protein aggregates also promote human malignancies. In collaboration with the Max Planck Institute for Multidisciplinary Sciences, Department of NMR-based Structural Biology, we explore the vulnerability of aggregated proteins in gastrointestinal cancers.